Sfp1 regulates yeast cell growth and division through multiple promoter binding modes

Understanding how transcriptional programs help to coordinate cell growth and division is an important unresolved problem. Here we report that the nutrient- and stress-regulated transcription factor Sfp1 is rate-limiting for expression of a large suite of genes involved in yeast cell growth, including ribosomal protein, ribosome biogenesis, and snoRNA genes. Remarkably, the spectrum of Sfp1 transcription effects is concordant with a combination of chromatin immunoprecipitation and chromatin endogenous cleavage binding analyses, which together provide evidence for two distinct modes of Sfp1 promoter binding, one requiring a co-factor and the other a specific DNA-recognition motif. In addition to growth-related genes, Sfp1 binds to and regulates the promoters of key G1/S regulon genes and that of MRS6, whose product regulates Sfp1 nuclear localization. Our findings suggest that Sfp1 acts as a master regulator of cell growth and cell size by coordinating the expression of genes implicated in mass accumulation and cell division. Sfp1 occupancy as well as RNA Polymerase II binding was measured upon nuclear depletion or overexpression of Sfp1

解析转录程序如何协同调控细胞生长与分裂，是一个尚未解决的重要科学问题。本研究发现，受营养与应激调控的转录因子Sfp1是酵母细胞生长相关大量基因表达的限速因子，这些基因涵盖核糖体蛋白、核糖体生物发生及核仁小RNA（snoRNA）编码基因。值得注意的是，Sfp1介导的转录调控效应谱与染色质免疫沉淀（chromatin immunoprecipitation）及染色质内源切割结合分析的结果高度一致，这些联合分析为Sfp1启动子结合的两种不同模式提供了证据：一种模式需要辅因子参与，另一种则依赖特定的DNA识别基序。除生长相关基因外，Sfp1还可结合并调控关键G1/S调控子基因的启动子，以及MRS6的启动子；MRS6的编码产物可调控Sfp1的核定位。本研究结果表明，Sfp1通过协同调控与物质积累及细胞分裂相关的基因表达，作为细胞生长与细胞体积的核心调控因子发挥功能。本研究通过对Sfp1进行核耗竭或过表达处理，检测了Sfp1的染色质结合占有率以及RNA聚合酶II（RNA Polymerase II）的结合水平。